What Does the Future Hold for Yellow Fever Virus? (I)

Abstract

Abstract:The recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. YFV had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes aegypti mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s) and vertebrate host(s). Outbreaks recently reported in Central Africa (2015)(2016) and Brazil (since late 2016), reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions regarding the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease

“…South American I is the predominant YFV genotype in Brazil, possessing five distinct lineages 1A-1E [17,18]. Until the middle of the 1990s, the old lineages (1A, 1B, and 1C) co-circulated in South America but were then replaced by the modern ones, 1D and 1E [8,[17][18][19]. Lineage 1E is responsible for the recent YF outbreaks in Brazil (2016 to 2019), and it was probably originated from YF endemic areas in North Brazil [20,21].…”

“…Since all South American NHP are highly susceptible to YFV infection, and epizootics often precede human cases, NHP can be used as sentinels during surveillance programs [8]. In 1999, the Brazilian Ministry of Health (MOH) launched the Epizootics Surveillance Program aiming at the investigation of NHP epizootics and entomological surveillance [32].…”

“…Humans are considered incidental hosts for YFV. The virus is maintained by different cycles in tropical and subtropical regions of sub-Saharan Africa and South America via transmission among different mosquitoes and NHP [2,[7][8][9]. Most of the experimental studies with YFV were performed with Old World NHP, but little is known about YF and the pathogenesis in Neotropical NHP.…”

What Does the Future Hold for Yellow Fever Virus? (II)

“…However, the NS5 coding sequence and the 3'UTR are still used on some occasions [134,138]. As detailed in the first section of this review, there is a strong association between the phylogenetic and the geographic clustering of YFV strains so genotypes correspond to specific geographic areas that rarely overlap [109]. This is suggestive of a predominant role of in situ evolution in shaping YFV diversity, consistent with the maintenance of YFV in a primarily "sylvatic" mode of transmission [139].…”

“…They suggest that a preponderant role of transovarial transmission (TOT) within mosquitoes in the maintenance of the virus could be implicated as such a mechanism, where the virus may remain quiescent in mosquito eggs for many months, would decrease the replication rate of the virus [105]. As detailed in the first part of this review several elements indicate that the TOT mechanism is not likely to play a significant role in YFV maintenance, neither in Africa nor in South America [109].…”